Nanostructured Metal Complexes for Targeted Delivery in Alzheimer’s Therapy
نویسندگان
1 Department of General Medicine, Vels Medical College and Hospital, Vels Institute of Science, Technology and Advanced Studies, Manjankaranai, Thiruvallur - 601 102, Tamil Nadu, India
2 Department of Pharmacy Practice, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad U.P, 244001, India
3 Department of Pharmaceutics, School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
4 Department of Pharmacognosy, School of Pharmacy, Vishwakarma University, Kondhwa, Pune, Maharashtra 411048, India
5 Department of Pharmaceutical Analysis, Malla Reddy Institute of Pharmaceutical Sciences, Maisammaguda, Dhulapally, Secunderabad 500100, Hyderabad, India
6 Department of Analytical Research and Development, Cambrex, Charles City, Iowa- 50616, USA
7 Koneru Lakshmaiah Education Foundation, Vaddeswaram, Vijayawada, Andhra Pradesh, India
8 Department of Pharmacology, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies, Pallavaram, Chennai - 600 117, India
doi
10.48309/jaoc.2026.549118.1339چکیده
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) aggregation, tau hyperphosphorylation, metal-ion dyshomeostasis, oxidative stress, and chronic neuroinflammation, all of which contribute to cognitive decline and neuronal loss. Increasing evidence highlights the critical role of aberrant transition metals, such as copper, iron, zinc, and aluminum, in accelerating protein misfolding and redox imbalance, thereby amplifying disease pathology. Conventional therapies have shown limited efficacy due to poor blood–brain barrier (BBB) penetration, lack of specificity, and inability to target multiple pathogenic pathways simultaneously. Emerging nanostructured metal complexes offer a novel multimodal approach that combines tunable physicochemical properties, versatile ligand functionalization, and incorporation into advanced nanoformulations (e.g., liposomes, dendrimers, and polymeric nanoparticles). These systems enhance BBB permeability, enable targeted delivery, provide controlled drug release, and reduce systemic toxicity. Mechanistically, they inhibit Aβ aggregation, modulate tau hyperphosphorylation, chelate excess metal ions, and provide antioxidant and anti-inflammatory neuroprotective effects. Copper-, iron-, zinc-, ruthenium-, and platinum-based complexes have demonstrated promising preclinical efficacy, particularly when integrated into ligand-decorated, stimuli-responsive, or multifunctional theranostic platforms. Synergistic co-delivery with small molecules or genetic materials further expands the therapeutic versatility. The remaining challenges are BBB navigation, precision targeting, scalable manufacturing, and regulatory approval. Leveraging precision medicine, artificial intelligence, and computational modeling can accelerate rational design, optimization, and clinical translation. Overall, nanostructured metal complexes represent a cutting-edge, multitargeted, and clinically translatable strategy for AD therapy.
